3-phenylsalicylamide



United States Patent 3-PHENYLSALICYLAMIDE Melville Sahyun and John A. Faust, Santa Barbara, Calif.,

assignors, by mesne assignments, to Cutter Lahoreitories, Inc., Berkeley, Calif., a corporation of Caliorma No Drawing. Application March 11, 1954, Serial No. 415,696

1 Claim. (Cl. 260-559) This invention relates to 3-phenylsalicylamide and a process whereby such compound may be prepared.

The compound of the present invention is a crystalline solid, insoluble in water, but soluble in ethanol and ether. This compound, in preliminary pharmacological testing, has indicated outstanding utility as an analgesic agent.

The compound of the present invention may be readily prepared by an ammonolysis type reaction involving the interaction of methyl 3-phenylsalicylate and ammonia. The ammonia and methyl 3-phenylsalicylate are contacted in the presence of a suitable solvent and in a suitable container for an extended period, usually at least two days, however, longer times may be used. If pressure apparatus is used, this time may be decreased. Representative solvents which may be employed include, for example, methanol, ethanol, isopropanol, et cetera. The resulting 3-phenylsalicylamide is separated from the resulting mixture in conventional manner, as by removal of unreacted ammonia and solvent and recrystallization.

The following example more specifically describes the method of the present invention, but it is not be construed as limiting the invention thereto.

Example Twenty-two and eight-tenths (22.8) grams (0.1 mole) of methy 3-phenylsalicylate and 200 milliliters of methanol were admixed in a citrate bottle and the resulting admixture titrated with ammonia. The citrate bottle was immediately capped and the contents permitted to stand at room temperature for six days, after which time the methanol and excess ammonia were removed by distillation, leaving a brown, solid residue. The solid material was taken up in isopropanol and then purified with ac- Patented June 19, 1956 tivated charcoal. Upon dilution of the thus-clarified isopropanol solution with Water, 16.2 grams (76 percent of the theoretical yield) of colorless needles of 3-phenylsalicylamide, melting at 142-143 degrees centrigrade, was

6 obtained. Reworking of the mother liquor increased the yield to ninety percent of the theoretical.

Analysis:

Calculated percent N, 6.5 Found do 6.37

This material has a molecular Weight of 213.23 and a corrected purified melting point of 1395-1405 degrees centigrade.

Pharmacological studies in animals of 3-phenylsalicylamide when compared against two well-known analgesic agents gave the following results:

Table Therapeutic Com Lethal Efiective Analgetic pound Index Dose.o Doseso Degree LDED/EDEU Aeetyl Salicylic Acid- 500 350 Sligh 1. 4

Salicylamide 480 175 do 3. 0 3- Phenylsalicylamide 1, 500 350 Pronounced. 4. 0

This application is a continuation-in-part of our prior application Serial 292,581, filed June 9, 1952, now abancloned.

Various modifications may be made in the method and compounds of the present invention Without departing from the spirit or scope thereof and it is to be understood that We limit ourselves only as defined in the appended OTHER REFERENCES Graebe et al.: Liebigs Annalen, vol. 284 (1895), p. 322.

Way et a1.: J. Pharmacol. Exptl. Therap., vol. 108, August 1953, (received February 27, 1953), pp. 450-60. 

